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Objective measurement of physical activity via accelerometers or other wearable devices that measure both duration and intensity over longer periods, in future trials would assist in assessing adherence to the intervention and monitoring cross-contamination. More frequent assessments of actual dietary intake, for example with a daily food diary, would provide better assessment of changes in dietary intake throughout the study period. Of particular concern, animal models have suggested that ecstasy acts as selective serotonergic neurotoxin in several areas of the brain. In humans, neuroimaging studies using positron emission tomography scans have shown reduced 5-HT transporter densities as well as increased 5-HT 2A receptor binding, even among abstinent ecstasy users in several cortical regions, including the hippocampus, frontal, occipital, and temporal areas of the cortex. Such findings suggest damage to the serotonergic system even with moderate levels of ecstasy use, such that SERT downregulates while 5-HT 2A upregulates. In addition, a dose-dependent relationship between decreased SERT densities and increased lifetime ecstasy use has been reported. It has been suggested that the hippocampus may be particularly sensitive to ecstasyassociated neurotoxicity. Among rats given MDMA, serotonin neurotoxicity was greater in the hippocampus than in other brain regions surrounding the temporal lobe, such as the neocortex and parietal lobe. Consistent with this finding in animals, adolescent ecstasy users demonstrated abnormal hippocampal activation to a verbal working memory fMRI task. Additionally, Daumann and colleagues examined brain activation during an fMRI task among adult abstinent ecstasy users and noted abnormal activation patterns in frontal and temporal regions among those with histories of heavy use versus those with moderate use and nonusers. Among users, results indicated correlations between prefrontal and parietal hypometabolism and learning and recall deficits, and between mediotemporal hypometabolism and recognition deficits. With respect to performance on a prose recall task, there has been an inability to replicate the deficits found among ecstasy users in Morgan et al.’s sample. Consistent with differences in the developmental trajectory of specific brain regions between men and women, particularly the hippocampus, it may be possible that gender moderates the effects of ecstasy on memory. Furthermore, gender differences in underlying 5HT functioning have been reported. For example, low cerebral spinal fluid 5HIAA has been associated with increased risk for serotonin-related diseases. Some studies have reported that levels of the serotonin metabolite differ as a function of gender and genetic interactions, with one mechanism being the effect of estrogen on signal transduction and gene expression affecting serotonin functioning. Allott and Redman reviewed the role of gender in ecstasy effects and concluded that female users appear more vulnerable to variability in 5-HT functioning as well as to short term dose-dependent psychological and physical symptoms, while male users tend to show increased acute physiological effects. However, not all studies examined differences in dose between genders, and few neurocognitive studies have examined potential gender differences. Reneman et al. reported greater reductions in SERT binding among female compared to male ecstasy users, after controlling for verbal intelligence, age, comorbid alcohol, nicotine and marijuana use, and premorbid Axis I psychiatric disorders. Of note, this study examined ecstasy dose between moderate- and heavy-using groups of men and women, finding that men within the heavy-using group reported increased exposure as compared to heavy-using women as measured by both number of tablets as well as dosage. In contrast, Bolla et al. found that male ecstasy users demonstrated increased dose-dependent deficits on verbal and visual memory than female users. The goal of the present study was to examine whether ecstasy use and gender interact in predicting components of verbal memory including immediate recall, proactive interference, short delayed recall, long delayed recall, discriminability, and retention after controlling for important demographic variables such as ethnicity, premorbid verbal ability, and family history of substance use disorders.

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